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This review article will consider the utility of calculated globulin (CG) as a simple and unbiased screening tool for immunodeficiencies. We review literature indicating that CG can serve as an inexpensive and routinely performed proxy for immunoglobulin levels due to their established correlation. We also set out a workflow for the implementation of CG into clinical practice and discuss optimal approaches to embedding into laboratory reporting systems, and integration of AI approaches could expedite diagnoses. Finally, we discuss the challenges and pitfalls of CG screening, including the need for established CG cutoffs\/action values across different patient age cohorts. Collaboration among biochemistry and immunology laboratories, clinicians, and patient organizations will be required to manage the logistics of effective broader implementation of CG screening into clinical practice.<\/jats:p>","DOI":"10.70962\/jhi.20260028","type":"journal-article","created":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T13:05:03Z","timestamp":1784207103000},"update-policy":"https:\/\/doi.org\/10.70962\/jhi.crossmarkpolicy","source":"Crossref","is-referenced-by-count":0,"title":["Implementing calculated globulin screening for immunodeficiencies: The benefits and challenges"],"prefix":"10.70962","volume":"2","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7394-6804","authenticated-orcid":true,"given":"Stephen","family":"Jolles","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/04fgpet95","id-type":"ROR","asserted-by":"publisher"}],"name":"Immunodeficiency Centre for Wales, University Hospital of Wales 1 , Cardiff,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6817-0573","authenticated-orcid":true,"given":"Cecilia","family":"Poli","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/028ynny55","id-type":"ROR","asserted-by":"publisher"}],"name":"Program of Immunogenetics and Translational Immunology, Faculty of Medicine, Cl\u00ednica Alemana Universidad del Desarrollo 2 , Santiago,","place":["Chile"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2549-0678","authenticated-orcid":true,"given":"Nicholas L.","family":"Rider","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02rsjh069","id-type":"ROR","asserted-by":"publisher"}],"name":"The Carilion Clinic 3 Department of Health Systems & Implementation Science Virginia Tech Carilion School of Medicine, Department of Pediatrics, Section of Allergy-Immunology, , Roanoke, VA,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-6639-4604","authenticated-orcid":true,"given":"Gabriela","family":"Negritu","sequence":"additional","affiliation":[{"name":"CSL AG 4 , Bern,","place":["Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-5801-0571","authenticated-orcid":true,"given":"Til","family":"Rendschmidt","sequence":"additional","affiliation":[{"name":"CSL GmbH 5 , Marburg,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1069-3117","authenticated-orcid":true,"given":"Antonio","family":"Condino-Neto","sequence":"additional","affiliation":[{"name":"Jeffrey Modell Diagnostic and Research Center 6 , S\u00e3o Paulo,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[2026,7,16]]},"reference":[{"key":"2026071609045811900_bib1","doi-asserted-by":"publisher","first-page":"1293","DOI":"10.1007\/s10875-022-01274-w","article-title":"Inborn errors of immunity on the Island of Ireland - a cross-jurisdictional UKPID\/ESID registry report","volume":"42","author":"Ryan","year":"2022","journal-title":"J. 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